Abstract

Fatty acid-binding proteins (FABPs) are cytoplasmic chaperones involved in intracellular lipid transport. Through their interactions with many transcription factors, these proteins affect several pathways in macrophages such as cholesterol trafficking and the immune and stress response pathways. Fatty acid-binding protein expression by macrophages and adipocytes dramatically modulates the pathological processes of obesity, diabetes and atherosclerosis. The highly homologous FABP isoforms, aP2 and Mal1, are expressed by macrophages in atherosclerotic lesions. We have previously shown that macrophage deficiency of aP2 reduces atherosclerosis through its effects on inflammation and cholesterol homeostasis (Nature Medicine 2001, 7:699). These effects were later shown to be caused via the impact of aP2 on PPARγ (JBC 2005, 280:12888). However, the impact of Mal1 expression in atherosclerosis remains unknown. Aim of Study: To investigate the role of the fatty acid-binding protein, Mal1, in macrophage biology and atherosclerosis Conclusion - Deficiency of the fatty acid-binding protein, Mal1, reduces early atherosclerotic lesions. Additionally, Mal1 is a key regulator of PPARγ activity, ER stress response, and inflammatory activity in macrophages. These results identify Mal1 as a potential therapeutic target in atherosclerosis.